5-phenyl-7-chloro-1h-1,5-benzodiazepin e-2,4-(3h,5h)-diones

ABSTRACT

WHEREIN R1 is hydroxy-alkyl of two to four carbon atoms; haloalkyl of two to four carbon atoms; di(alkyl of two to four carbon atoms)amino-alkyl of two to four carbon atoms; gamma piperidino-propyl; alkoxy of one to two carbon atoms - alkyl of one to four carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkyl of one to four carbon atoms; (alkyl of one to two carbon atoms) mercapto-alkyl of one to four carbon atoms; straight or branched alkenyl of three to five carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkenyl of two to four carbon atoms; or halo-alkenyl of two to four carbon atoms; THE COMPOUNDS ARE USEFUL AS PSYCHOSEDATIVES AND ANTICONVULSIVES.   Compounds of the formula

United States Patent Weber et al.

[54] 5-PHENYL-7-CHLORO-1H-l,5-

BENZODIAZEPIN E-2,4-(3H,5H)- DIONES [73] Assignee: Boehringer lngellheimG.m.b.H., ln-

gqlhe m enlihinezfi r eny 221 Filed: Feb. 1, 1971 211 Appl.No.: 111,716

Related u.s. Application Data [63] Continuation-impart of Ser. No.89,482, Nov.

13, 1970, which is a continuation-in-part of Ser. No. 703,188, Feb. 5,1968, abandoned.

[30] Foreign Application Priority Data Feb. 7, 1967 Germany ..B 91071Jan. 18, 1968 Germany ..B 96281 Jan. 18, 1968 Germany ..B 92682 [52] US.Cl. ..260/239.3 B, 424/244 [51] Int. Cl. ..C07d 53/04 [58] Field ofSearch ..260/293.3 B

[151 3,684,798 [451 Aug. 15, 1972 [56] References Cited OTHERPUBLICATIONS Buchi et a1., Helo. Chim Acta Vol. 39, pages 95 2- 963(1956).

Primary Examiner-Henry R. Tiles Assistant ExaminerRobert T. BondAtrorneyHammond & Littell ABSTRACT Compounds of the formula R1 0 91ktCH2 CI R is hydroxy-alkyl of two to four carbon atoms; haloalkyl of twoto four carbon atoms; di(alkyl of two to four carbon atoms)amino-alkylof two to four carbon atoms; 'y-piperidino-propyl; alkoxy of one to twocarbon atoms alkyl of one to four carbon atoms; (alkoxy of one to twocarbon atoms)carbonyl-alkyl of one to four carbon atoms; (alkyl of oneto two carbon atoms) mercapto-alkyl of one to four carbon atoms;straight or branched alkenyl of three to five carbon atoms; (alkoxy ofone to two carbon atoms)carbonyl-alkenyl of two to four carbon atoms; orhalo-alkenyl of two to four carbon atoms;

the compounds are useful as psychosedatives and anms 8 Claims, NoDrawings I i ,N l l xHz 01 N 65H; (I)

wherein R is hydroxy-alkyl of two to four carbon atoms; haloalkyl of twotofour carbon atoms; di(alkyl of two to four carbon atoms)arnino-alkylof two to four carbon atoms; y-piperidinopropyl; alkoxy of one to twocarbon atoms-alkyl of one to four carbon atoms; (alkoxy of one to twocarbon' atoms )carbonyl-alkyl of one to four carbon atoms; (alkyl of oneto two carbon atoms)mercapto-alkyl of one to four carbon atoms; straightor branched alkenyl of three to five carbon atoms; (alkoxy of one to twocarbon atoms)carbonyl-alkenyl of two to four carbon atoms; orhaIo-alkenyl of two to four carbon atoms.

The compounds according to the present invention may be prepared by anumber of different methods involving well known chemical principles,among which the following have proved to be particularly convenient andefiicient:

Method A By cyclizing an N-phenyl-N-(Z-amino-S-chlorophenyl)-malonicacid lower alkyl ester amide of the formula m uHr (III) wherein R, hasthe same meanings as in formula I, with a malonic acid or alkylmalonicacid dihalide and, if

necessary, alkylating the cyclization product thus obtained in thel-position.

In method A the hydrolysis and ring closure proceed smoothly and withgood yields in an acid as well as an alkaline medium, preferably in thepresence of an alcoholic or aqueous alcoholic solvent; however, otherinert solvents such as tetrahydrofuran or dioxan, are also suitable;for-acid cyclization, .acetonitrile may also be used as the solvent.Mineral acids, and particularly hydrohalic acids, such as hydrochloricacid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphonic acidand perchloric acid are preferably used as acid cyclization agents.Examples of alkaline cyclization agents are sodium alcoholates andalkali metal hydroxides.

The reaction periods depend upon the quantity of acid or alkali employedand upon the type of solvent used; they vary between several hours andseveral days.

The preferred reaction temperatures are preferably between +20 C. andthe boiling point of the solvent which is used.

The preparation of an end product of the formula I, wherein R isunsubstituted or substituted alkyl, may be carried out in various ways.One may, for instance, start from a compound of formula I wherein R ishydrogen and exchange the same for an alkyl group with the aid of acustomary alkylating agent, such as an alkyl halide or an alkyl sulfate,such as a dialkylsulfate. For this purpose an alkali metal salt of acompound of formula I is dissolved or suspended in a suitable solvent,the a] kylating agent is added to the solution or suspension, and thereaction mixture is heated. For the preparation of an end product of theformula I wherein R, is hydroxy-alkyl, a compound of the formula Iwherein R is hydrogenrnay be reacted with an alkyleneoxide in thepresence of a strong base, such as Triton-B. If the cyclization iscarried out under alkaline conditions, the alkylation of the l-positionmay also be effected after the cyclization is finished, without priorisolation of the l-unsubstituted benzodiazepine-2,4-dione cyclizationproduct. In this case the alkylating agent is added to the cyclizationreaction solution containing the cyclization product, and the mixtureheated.

In method B the reaction is preferably carried out in the presence of asuitable inert organic solvent, such as benzene, toluene, xylene,tetrahydrofuran, dioxan or dimethylformamide, at room temperature or,more advantageously, at the boiling point of the particular solventwhich is used. In some cases the addition of a tertiary organic base,such as pyridine, has proved to have a favorable influence upon thecourse of the reaction. An end product of the formula I, wherein R ishydrogen, may be subsequently alkylated, as described in conjunctionwith method A.

If, in a compound of the formula I, R, is hydroxyalkyl, the hydroxylgroup may subsequently be replaced by a halogen atom by treatment with athionyl halide in the presence of dimethylformamide, or converted intoan alkoxy group by treatment with a diazoalkane in the presence ofborontrifluoride etherate.

If R, in a compound of the formula I is dialkylaminoalkyl, it ispossible to introduce a double bond into the alkyl moiety byquaternization and splitting off trialkylarnine.

Furthermore, in a compound of the general formula I, wherein R isalkenyl, this substituent may be partially or completely hydrogenated byknown methods.

The N-phenyl-N-( 2-amino-5-chloro-phenyl)- malonic acid lower alkylester amides of the formula 11 used as starting materials for method Aare also novel. They may be prepared by reacting a correspondinglysubstituted N-phenyl-N-( 2-nitro 5-chloro-phenyl amine with a malonicacid monoalkyl ester halide to obtain anN-phenyl-N-(2-nitro-5-chloro-phenyl)- malonic acid alkyl ester amide,and subsequently reducing the nitro group according to the followingreaction sequence:

O Alkyl Thus, the preparation of an N-phenyl-N-(2-nitro-5-chloro-phenyD-malonic acid alkyl ester amide of the formula IV iscarried out, for example, by heating a solution ofN-phenyl-N-(2-nitro-5-chloro-phenyl)- amine in a suitable solvent, suchas benzene, toluene or xylene, with a malonic acid ester halide, wherebythe nitro compound IV is always obtained with good yields (80 percent)and in crystalline form.

The subsequent reduction of compound IV may be effected by nascent orcatalytic hydrogenation, for example, by hydrogenation with Raney-nickelor with a mixture of iron and glacial acetic acid.

For the cyclization to form the 5-phenyl-7-chloro--lH-l,5-benzodiazepine-2,4end product of the formula I it is notabsolutely necessary to start from an isolated compound of the formula11; instead, the solution containing the hydrogenated intermediateproduct 11 may directly be treated with the cyclization agents mentionedabove, after removal of the catalyst.

The starting compounds of the formula III may be prepared byconventional methods, for example, by catalytic reduction of thecorresponding 2-nitrodiphenylamine, or analogous to the method describedin Chem. Berichte, Volume 34, page 4204 1902), and Volume 37, page 552(1904), that is, by cyclizing a 2- aminodiphenyl-amine with formic acid,alkylating at the nitrogen atom in the cyclization product by means ofan alkyl iodide, and subsequently splitting the ring with an alkali.

The following examples further illustrate the present invention and willenable others skilled in the art to understand it more completely. Itshould be understood,

however, that the invention is not limited solely to the particularexamples given below.

EXAMPLEl 1-( BJ-Iydroxy-ethyl )-5-phenyl-7-chlorol H- l ,5-benzodiazepine-2,4-(3H,5H)-dione by method A A mixture consisting of28.6 gm (0.1 mol) of 5-phenyl-7-chloro-lH-l,5-benzodiazepine-2,4-(3H,5H)- dione, 500 ml of methanol, 25 ml of water, 10-15 ml ofethyleneoxide and 1 ml of TritonBtmethanolic 35percent solution ofbenzyltri'methylammonium hydroxide) was stirred at room temperature forabout 8 hours. Thereafter, the clear solution formed thereby wasevaporated, the residue was taken up in methylene chloride, and theresulting solution was extracted with water, dried and evaporated. Theresidue was recrystallized from ethanol, yielding 25.6 gm (78 percent oftheory) of the colorless crystalline compound of the formula HOCH2CH2 OI /NG\ O I OH: 01

N 'JeHA \O having a melting point of 208-210 C.

EXAMPLE 2 1-(B-Methoxy-ethyl)-5phenyl-7-chloro- 1 H- 1 ,5benzodiazepine-2,4-(3H,5H)-dione by method A 28.6 gm (0.1 mol) of5-phenyl-7-chloro-1H-l,5- benzodiazepine-2,4-(3H,5H)-dione weresuspended in 750 ml of absolute tetrahydrofuran, 5 gm of a 50 percentdispersion of sodium hydride in tetrahydrofuran were added to thesuspension and the mixture was stirred for 2 hours at room temperature,whereby everything went into solution. 21-28 gm (0.15 0.2 mol) of,B-bromo-ethyl methyl ether were then added to the solution, and theresulting mixture was refluxed for 15-20 hours. Thereafter, the reactionsolution was evaporated in vacuo, the residue was admixed with water,and the aqueous mixture was extracted with methylene chloride. Themethylene chloride extract was vacuum-filtered to remove insolublecomponents, the filtrate was evaporated, and the residue wasrecrystallized from isopropyl ether, yielding 22 gm (64 percent oftheory) of the compound of the formula HzCO-CHz-CHz O Calls 0 having amelting point of 178-180 C.

EXAMPLE 3 was prepared from 7-chloro-5-pheny1-lH-l,5-benzodiazepine-2,4-( 3H,5H)-dione and allyl bromide.

EXAMPLE 4' Using a procedure analogous to that described in Example 2,1-[isopenten-(4' )-yll ]-7-chloro-5-phenyllH-l ,5 -benzodiazepine-2,4-(3H,5H )-dione, m.p. l f th iormula.

i from 7-chloro-5-phenyl-lH-l,5- benzodiazepine-2,4-(3H,5l-l)-dione andisopenten-(4)- yl-l bromide.

EXAMPLE 5 Using a procedure analogous to that described in Example 2,1-dimethylallyl-7-chloro-5-phenyl-1l-I-1,5-benzodiazepine-2,4-(3H,5H)-dione, m.p. 154-l56 19* h mula JuHu wasprepared from 7-chloro-5phenyl-lH-l,5-

bezodiazepine-2,4-(3H,5H)-dione and dimethylallyl bromide.

EXAMPLE 6 Using a procedure analogous to that described in Exwasprepared from 7-chloro-5-phenyl-lH-l,5- benzodiazepine-2,4-(3H,5H)-dioneand chloroallyl bromide.

EXAMPLE 7 Using a procedure analogous to that described in Example l,l-( l -hydroxy-propyl-2 )-7-chloro-5-phenyl- 1H- 1,5-benzodiazepine-2,4-( 3H,5H)-dione, mp. 192 195 C., of the formulaClla was prepared from 7-chloro-5-phenyl-lH-l,5-benzodiazepine-2,4-(3l-l,5l-l)-dione and propyleneoxide.

EXAMPLE8 Using a procedure analogous to that described in Example 2,l-(/3-methoxy-ethyl)-7-chloro-5-phenyl-1H- l,5-benzodiazepine-2,4-(3H,5I-l)-dione, m.p. 175-178 C., of the formula ts 5555a 513;; ll 7'h15i5 s" 5iiI i-in i ,s benzodiazepine-2,4-(3H,5H)-dione andB-methoxyethyl bromide.

EXAMPLE 9 EXAMPLE 10 Using a procedure analogous to that described inExample 2, 1-(,B-ethoxyethyl)-7-chloro-5-phenyl-1H-l,5-benzodiazepine-2,4-(3H,5H)-dione, m.p. -l37 C., was prepared from7-chloro-5-phenyl-1H-l,5- benzodiazepine-2,4-(3H,5H)-dione andB-ethoxyethyl bromide.

EXAMPLE ll Using a procedure analogous to that described in Example l,1-(B-dimethylamino-ethyl)-7-chloro-5-phenyl-lH-l,5-benzodiazepine-2,4-(3H,5H)-dione, m.p. l48150 C.; of the formula wasprepared from 7-chloro-5-phenyl-1H-1,5- benzodiazepine-2,4-(3H,5H)-dioneand B- dimethylamino-ethyl bromide.

EXAMPLE 12 Using a procedure analogous to that described in Example 2,1-(/3-diethylamino-ethyl)-7-chloro-5-phenyl- EXAMPLE 13 Using aprocedure analogous to that described in Example 2,l-(ethoxycarbonylmethyl)-7-chloro-5-phenyll H-l ,5-benzOdiazepine-2,4(3H,5H)-dione, m.p. 159-l 60 C., of the formula was prepared from7-chloro-5-Phenyl-1H-l ,5- benzodiazepine-2,4-(3H,5H)-dione andethoxycarbonylmethylbromide.

EXAMPLE 14 Using a procedure analogous to that described in Example 2,l-('y -chloro-n propyl)-7-chloro-5-phenyl)-lI-ll,5-benzodiazepine-2,4-(3H,5H)-dione,m.p. l56l 58 C., of the formuladlCHzCH-2CH2 o M CH1 o1 flHfl g was prepared fF6 fi*IEii1Z5- 11E1T1-1H-1,5- benzodiazepine-2,4-(3H,5H)-dione an 1,3-dichloropropane.

EXAMPLE 15 Using a procedure analogous to that described in Example 2,l-(methoxycarbonyl-allyl)-7chloro-5-phenylll-l-l ,5-benzodiazepine-2,4-(3H,5H)-dione, m.p. l 72174 C., of the formulabenzodiazepine-2,4-(3H,5H)-dione and methoxycarbonyl-allyl bromide.

Example 16 Using a procedure analogous to that described in Example 2,l-(B-ethylmercapto-ethyl)-7-chloro-5-phenyl l H- 1,5-benzodiazepine-2,4-( 3H,5H)-dione, m.p. 129-131 C., ofthe formula EEKwas prepared from 7-chloro-5-phenyl-1l-1-1,5- b enzodiaiepine2,4-(3H,5H)-Dione and B-ethylmercapto-ethyl bromide.

EXAMPLE 17 Using a procedure analogous to that described in Example 2,1-('y-hydroxy-n-propyl)-5-phenyl-7-chloro-11-1-1,5-benzodiazepine-2,4-(3H,5H)-dione, mp. 21 1-2l3 C., was preparedfrom 5-phenyl-7-chloro-1 H-l,5-benzodiazepine-2,4-(3H,5H)-dione and 3-chloro-propanol.

EXAMPLE 18 Using a procedure analogous to that described in Example 2,l-('y-piperidino-n-propyl)-5-phenyl-7-chlorolH-1,5-benzodiazepine-2,4-(3H,5H)-dione,m.p. 42- 459 .q lrqf mu au was prepared from 5-phenyl-7-chloro-lH-l ,5-benzodiazepine-2,4-(3H,5H)-dione and piperidino-npropyl bromide.

The compounds according to the present invention, that is, thoseembraced by formula 1 above, have useful phannacodynamic properties.More particularly, they exhibit very efl'ective psychosedative(tranquilizing) and anticon-vulsive activities in warm-blooded animals,such as mice, rats and dogs, coupled with low toxicity.

Particularly efiective are compounds of the formula 1 wherein R isw-hydroxy-alkyl, w-alkoxy-alkyl or dialkylarnino-alkyl, and especiallyl-(B-hydroxy-ethyl)-5- phenyl-7-chl0ro-lH-1,5-benzodiazepine-2,4-(3 H,5Hdione, 1-( methoxy--methyl)-5-phenyl-7-chlorol H-1,5-benzodiazepine-2,4-(3H,5H)-dione and 1(3- methoxy-ethyl)-5-phenyl7-chlorol H,- 1 ,5 benzodiazepine-2,4-(3H,5H)-dione.

For pharmaceutical purposes the compounds according to the presentinvention are administered to warm-blooded animals perorally orparenterally as active ingredients in customary dosage unitcompositions, that is, compositions in dosage unit form consistingessentially of an inert pharmaceutical carrier and one effective dosageunit of the active ingredient, such as tablets, coated pills, capsules,wafers, powders, solutions, suspensions, emulsions, syrups,suppositories and the like. One effective dosage unit of the compoundsaccording to the present invention is from 0.0166 to 0.833 mgm/kg bodyweight, preferably 0.0833 to 0.42 mgrn/kg, and the daily dose rate isfrom 0.166 to 2.5 mgm/kg.

The following examples illustrate a few dosage unit compositionscomprising a compound of the instant inspecified.

EXAMPLE l9 Coated pills The pill core composition was compounded fromthe following ingredients:

1,S-benzodiazepine-Z,4-(31'1,51-1)-dione 10.0 parts Lactose 28.5 partsCorn starch 15.0 parts Gelatin 1.0 parts Magnesium stearate 0.5 partsTotal 55.0 parts Compounding procedure:

The benzodiazepinedione compound was intimately admixed with the lactoseand the corn starch, the mixture was moistened with an aqueous percentsolution of the gelatin, the moist mass was forced through a 1 mm-meshscreen, and the granulate obtained thereby was dried at 40 C. and againpassed through the screen. The dry granulate was admixed with themagnesium stearate, and the mixture was pressed into 55 mgm-pill cores,which were subsequently coated with a thin shell with the aid of anaqueous suspension of sugar,talcum, titanium dioxide and arabic, and thecoated pills were polished with beeswax. One coated pill contained 10mgm of the benzodiazepinedione compound and, when administered to awarm-blooded animal of about 60 kg body weight in need of suchtreatment, produced very good tranquilizing and anticonvulsive effects.

The same I results were obtained when the benzodiazepinedione compoundin the above pill core composition was replaced by an equal amount ofone of the following benzodiazepinediones:

a. l-(y-Hydroxy-n-propyD-5-pheny1-7-chlorol H-1,5-benzodiazepine-2,4(3H,5H)-dione;

1-(B-Methoxy-ethyl)-5-phenyl-7-chloro- 1H- 1 ,5-benzodiazepine-2,4-(3H,5H)-dione; or c.1-(Dimethylamino-ethyl)-5-phenyl-7-chloro-1H- l ,5-benzodiazepine-2,4(3H,5H)-dione.

EXAMPLE 20 Suppositories The suppository composition was compounded fromthe following ingredients: 1-(-y-l-lydroxy-npropyl)-5-phenyl-7-chlorolH-l,5-benmdiazepine-2,4-(3H,5H)-dione 10.0parts Cocoa butter 1690.0 pans Total 1700.0 parts poured into cooledsuppository molds, each holding 1,700 mgm of the mixture. Onesuppository contained 10 mgm of the ,benzodiazepinedione compound and,when administered by the rectal route to a warmblooded animal of about60 kg body weight in need of such treatment, produced very goodtranquilizing and anticonvulsive efi'ects.

Analogous results were obtained when any one of the otherbenzodiazepinediones embraced by formula I was substituted for theparticular benzodiazepinedione in Examples 19 and 20. Likewise, theamount of active ingredient in these illustrative examples may be variedto achieve the dosage unit range set forth above, and the amounts andnature of the inert pharmaceutical carrier ingredients may be varied tomeet particular requirements.

While the present invention has been illustrated with the aid of certainspecific embodiments thereof, it will be readily apparentto othersskilled in the art that the invention is not limited to these particularembodiments and that various changes and modifications may be madewithout departing from the spirit of the invention or the scope of theappended claims.

We claim:

1. A compound of the formula R1 0 l l wherein R is hydroxy-alkyl of twoto four carbon atoms; haloalkyl of two to four carbon atoms; di(alkyl oftwo to four carbon atoms)amino-a1kyl of two to four carbon atoms;y-piperidino'propyl; alkoxy of one .to two carbon atoms-alkyl of one tofour carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkyl ofone to four carbon atoms; (alkyl of one to two carbonatoms)mercapto-alkyl of one to four carbon atoms; straight or branchedalkenyl of three to five carbon atoms; (alkoxy of one to two carbonatoms)carbonyl-alkeny1 of two to four carbon atoms; or halo-alkenyl oftwo to four carbon atoms.

2. A compound according to claim 1, wherein R is w-hydroxy-alkyl of twoto three carbon atoms, 7- chloro-n-propyl, ,B-di( alkyl of one to twocarbon atoms)amino-ethyl, -piperidino-n-propyl, w-alkoxy of one to twocarbon atoms-alkyl of one to two carbon atoms, ethoxycarbonyl-methyl,B-ethylmercapto-ethyl, alkenyl of three to five carbon atoms,y-methoxycarbonyl-allyl or 'y-chloro-allyl.

3. A compound according to claim 1, wherein R is w-hydroxy-alkyl of twoto three carbon atoms, w-alkoxy of one to two carbon atoms-alkyl of oneto two carbon atoms or B-di(alkyl of one to two carbonatoms)amino-ethyl.

4. A compound according to claim 1, which is l-(B-hydroxy-ethyl-iphenyl-7-chloro-1H- 1 ,5- benzodiazepine-2,4-(3I-1,5H)-dione.

5. A compound according to claim 1, which is 1-( B-methoxy-ethyl)-5-phenyl-7-chlorol H- 1 ,5-benzodiazepine-2,4-(3H,5H)-dione.

6. A compound according to claim 1, which islbenzodiazepixze-ZA-(BHISl-lidione. methoxymethyl-S-phenyl-7-chloro-lH-l,5- 8. A compound according to claim 1, which is l-(B-benzodiazepine-2,4-( 3H,5H)-dione.dimethylamino-ethyl)-5-phenyl:7-chlorol H- l ,5-

7. A compound according to claim 1, which isl-(ybenmdlaZePme'2,4'(3H,5H)d1nehydroxy-n-propyl-5-phenyl-7-chloro-1H,l,5-5

2. A compound according to claim 1, wherein R1 is omega -hydroxy-alkylof two to three carbon atoms, gamma -chloro-n-propyl, Beta -di(alkyl ofone to two carbon atoms)amino-ethyl, gamma -piperidino-n-propyl, omega-alkoxy of one to two carbon atoms-alkyl of one to two carbon atoms,ethoxycarbonyl-methyl, Beta -ethylmercapto-ethyl, alkenyl of three tofive carbon atoms, gamma -methoxycarbonyl-allyl or gamma -chloro-allyl.3. A compound according to claim 1, wherein R1 is omega -hydroxy-alkylof two to three carbon atoms, omega -alkoxy of one to two carbonatoms-alkyl of one to two carbon atoms or Beta -di(alkyl of one to twocarbon atoms)amino-ethyl.
 4. A compound according to claim 1, which is1-( Beta-hydroxy-ethyl-5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione.5. A compound according to claim 1, which is 1-( Beta-methoxy-ethyl)-5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione.6. A compound according to claim 1, which is1-methoxymethyl-5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione.7. A compound according to claim 1, which is 1-( gamma-hydroxy-n-propyl-5-phenyl-7-chloro-1H,1,5-benzodiazepine-2,4-(3H,5H)-dione.8. A compound according to claim 1, which is 1-( Beta-dimethylamino-ethyl)-5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione.